This Developmental/Exploratory application proposes to explore the genetic basis of noise phobia, a common behavioral disorder in the domestic dog. The dog is an excellent model system for determining the genetic bases of behavior. Recent advances in canine genomics mean that the tools are in place for rigorous genetic analyses of canine behavioral traits. Naturally occurring anxiety syndromes, similar to many found in humans, are common in dogs, and often segregate in families. Anxiety disorders comprise the bulk of canine behavioral pathologies, and as such are clearly recognizable in canine patient populations. For our specific aims, we plan to carry out genetic analyses of canine noise phobia using pedigrees and case control samples in two pure breeds. We will obtain DNA samples from dogs among the ~60 members of an extended Border Collie noise phobia pedigree, as well as ~50 pairs of unrelated noise phobia cases and controls in each of two herding breeds, Border Collies and Australian Shepherds. We will determine the noise phobia phenotype using a detailed and clinically verified behavioral questionnaire, followed by genotyping with genome-wide SNP markers. Linkage analyses will be carried out with the family sample, and association analyses performed with the case-control sample. Successful analysis of a complex behavioral phenotype in the dog in a limited number of related breeds will provide the rationale for a more ambitious assessment of canine behavior phenotypes across numerous breeds. Additionally, translation of these findings into human anxiety disorder research will be facilitated. PUBLIC HEALTH RELEVANCE: Understanding noise phobia in dogs, taking advantage of the unique genetic structure of the domestic dog, and its behavioral similarities to humans may inform psychiatric research on human anxiety disorders. Elucidation of the biological systems underlying pathological behavior will heighten our general understanding of the underlying molecular biology of behavior, allowing the dog to contribute to this rapidly evolving field.